A sensitive and specific liquid-chromatographic assay for determination of ganciclovir in plasma and urine and its application to pharmacokinetic studies in the rabbit.
A liquid-chromatographic assay for the analysis of ganciclovir in plasma and urine is described. This assay involves the use of acyclovir, an antiviral drug structurally related to ganciclovir, as the internal standard. A two-step sample preparation method is used. After protein is precipitated with acetonitrile and the addition of diethyl ether, ganciclovir and the internal standard are back extracted into a small volume of aqueous ammonium phosphate, taking advantage of their relatively high water solubility. This isocratic method is specific and sufficiently sensitive to allow quantification of ganciclovir throughout the entire range of concentrations observed during therapeutic use of this antiviral drug. There was no interference from various over-the-counter and prescription drugs often prescribed to patients most likely to receive ganciclovir therapy. This assay was used to analyze plasma and urine samples obtained after intravenous administration of ganciclovir to rabbits. Biexponential decay of ganciclovir plasma concentration-time and urinary excretion rate-time profiles was observed, with a mean distribution half-life of 15.8 min and an elimination half-life of 96 min. The mean renal clearance, 9.0 ml/min per kg, exceeds the glomerular filtration rate in the rabbit, indicating that ganciclovir is actively secreted in the renal tubule. Similar results were obtained by determining the renal clearance at steady state during constant-rate intravenous infusion of ganciclovir.
Hedaya
M A
MA
Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis 55455.
Sawchuk
R J
RJ
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D015774:Ganciclovir / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D005919:Glomerular Filtration Rate; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008954:Models, Biological; D011786:Quality Control; D011817:Rabbits
D015774:Ganciclovir